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1.
Molecules ; 27(9)2022 May 04.
Article in English | MEDLINE | ID: covidwho-1820345

ABSTRACT

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7), phenolics (8-11), and flavonoids (12-17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-ß-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski's rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.


Subject(s)
COVID-19 , Euphorbia , COVID-19/drug therapy , Euphorbia/metabolism , Flavonoids/pharmacology , Glycoproteins , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
2.
RSC Adv ; 11(36): 22398-22408, 2021 Jun 21.
Article in English | MEDLINE | ID: covidwho-1815631

ABSTRACT

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. Natural products as sesame were reported to exhibit potential to protect from COVID-19 disease. In our study, the total methanolic extract of Sesamum indicum L. seeds (sesame) were led to isolation of seven known compounds, five lignan; sesamin 1, sesamolin 2, pinoresinol 3, hydroxymatairesinol 6, spicatolignan 7, together with two simple phenolic compounds; ferulic acid 4 and vanillic acid 5. All isolated compounds were evaluated in silico against three important SARS-CoV-2 protein targets; main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) which possessed crucial role in replication and proliferation of the virus inside the human cell. The results revealed that compound 6 has the high affinity against the three main proteins, specially towards the SARS-CoV-2 Mpro that exceeded the currently used SARS-CoV-2 Mpro inhibitor darunavir as well as, exhibiting a similar binding energy at SARS CoV-2 PLpro when compared with the co-crystallized ligand. This activity continued to include the RdRp as it displayed a comparable docking score with remdesivir. Inferiorly, compounds 1 and 2 showed also similar triple inhibitory effect against the three main proteins while compound 7 exhibited a dual inhibitory effect against SARS CoV-2 PLPro and RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds 1, 2, 3, 6, and 7 showed comparable binding stability inside the active site of each enzyme with ΔG values ranged from -4.9 to -8.8 kcal mol-1. All the compounds were investigated for their ADME and drug likeness properties, which showed acceptable ADME properties and obeying Lipinski's rule of five parameters. It can be concluded that the isolated compounds from sesame lignans could be an alternative source for the development of new natural leads against COVID-19.

3.
RSC advances ; 11(36):22398-22408, 2021.
Article in English | EuropePMC | ID: covidwho-1812594

ABSTRACT

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. Natural products as sesame were reported to exhibit potential to protect from COVID-19 disease. In our study, the total methanolic extract of Sesamum indicum L. seeds (sesame) were led to isolation of seven known compounds, five lignan;sesamin 1, sesamolin 2, pinoresinol 3, hydroxymatairesinol 6, spicatolignan 7, together with two simple phenolic compounds;ferulic acid 4 and vanillic acid 5. All isolated compounds were evaluated in silico against three important SARS-CoV-2 protein targets;main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) which possessed crucial role in replication and proliferation of the virus inside the human cell. The results revealed that compound 6 has the high affinity against the three main proteins, specially towards the SARS-CoV-2 Mpro that exceeded the currently used SARS-CoV-2 Mpro inhibitor darunavir as well as, exhibiting a similar binding energy at SARS CoV-2 PLpro when compared with the co-crystallized ligand. This activity continued to include the RdRp as it displayed a comparable docking score with remdesivir. Inferiorly, compounds 1 and 2 showed also similar triple inhibitory effect against the three main proteins while compound 7 exhibited a dual inhibitory effect against SARS CoV-2 PLPro and RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds 1, 2, 3, 6, and 7 showed comparable binding stability inside the active site of each enzyme with ΔG values ranged from −4.9 to −8.8 kcal mol−1. All the compounds were investigated for their ADME and drug likeness properties, which showed acceptable ADME properties and obeying Lipinski's rule of five parameters. It can be concluded that the isolated compounds from sesame lignans could be an alternative source for the development of new natural leads against COVID-19. Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332996

ABSTRACT

Background: COVID-19 outbreak resulted in negative mental health consequences such as depression, anxiety, and stress, particularly among health-care workers. Objective: To evaluate health care worker mental well-being and explore the reasons standing beyond their concerns and fears. Methods: From January to June 2021, we recruited 107 health care workers from psychiatric hospitals. The translated Arabic version COVID stress scale was used to assess their level of stress. The WHO Quality of Life - BREF score was used to assess their level of affection for their quality of life. Results: The majority of our sample (45.8%) was between the ages of 20 and 30. Females made up 37.8% of the group. The majority of them were infected during the first wave. The COVID Stress Scale (CSS) revealed that 21.5% of participants had no signs or symptoms of depression, while 55.1% had mild symptoms. Only 23.4% of our sample had moderate to severe symptoms. When categorised by domains, the mean CSS score was 12.21 ± 5.62 for danger subscale, 6.18 ± 4.07 for socioeconomic subscale, 8.44 ± 4.58 for xenophobia subscale, 7.99 ± 4.18 for contamination subscale, 5.87 ± 4.32 for traumatic subscale, and 11.13 ± 6.15 for compulsive subscale. The mean scores for the WHO QOL-brief score for physical aspect were 91.51 ± 21.5, 75.25 ± 12.84 for psychological aspect, 40.42 ± 8.52 for social aspect, and 96.26 ± 17.76 for environmental aspect. Conclusion: we discovered that health-care workers experienced high levels of stress, particularly during and after COVID -19 pandemic waves.

5.
Research Square ; 2022.
Article in English | EuropePMC | ID: covidwho-1786475

ABSTRACT

Background: COVID-19 outbreak resulted in negative mental health consequences such as depression, anxiety, and stress, particularly among health-care workers. Objective: To evaluate health care worker mental well-being and explore the reasons standing beyond their concerns and fears. Methods: From January to June 2021, we recruited 107 health care workers from psychiatric hospitals. The translated Arabic version COVID stress scale was used to assess their level of stress. The WHO Quality of Life - BREF score was used to assess their level of affection for their quality of life. Results: The majority of our sample (45.8%) was between the ages of 20 and 30. Females made up 37.8% of the group. The majority of them were infected during the first wave. The COVID Stress Scale (CSS) revealed that 21.5% of participants had no signs or symptoms of depression, while 55.1% had mild symptoms. Only 23.4% of our sample had moderate to severe symptoms. When categorised by domains, the mean CSS score was 12.21 ± 5.62 for danger subscale, 6.18 ± 4.07 for socioeconomic subscale, 8.44 ± 4.58 for xenophobia subscale, 7.99 ± 4.18 for contamination subscale, 5.87 ± 4.32 for traumatic subscale, and 11.13 ± 6.15 for compulsive subscale. The mean scores for the WHO QOL-brief score for physical aspect were 91.51 ± 21.5, 75.25 ± 12.84 for psychological aspect, 40.42 ± 8.52 for social aspect, and 96.26 ± 17.76 for environmental aspect. Conclusion: we discovered that health-care workers experienced high levels of stress, particularly during and after COVID -19 pandemic waves.

6.
BMJ Case Rep ; 14(3)2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1133189

ABSTRACT

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates.


Subject(s)
COVID-19/epidemiology , Ferritins/blood , Fever/etiology , Herpes Simplex/diagnosis , Pregnancy Complications, Infectious/diagnosis , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Female , Herpes Simplex/complications , Herpes Simplex/drug therapy , Herpesvirus 1, Human/isolation & purification , Humans , Infant, Newborn , Male , Pandemics , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/drug therapy , SARS-CoV-2 , Treatment Outcome
7.
Nat Prod Res ; 36(4): 994-998, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-894501

ABSTRACT

COVID 19; an infectious disease; firstly identified in December 2019 in Wuhan, China and has since spread globally, resulting in an ongoing pandemic. Searching for protease inhibitors is a challenging task in controlling COVID 19. Genus Ficus is known to be a rich source of phenolic compounds. Metabolic profiling of leaves methanolic extract of Ficus microcarpa (Moraceae) revealed nine compounds (1-9) mainly phenolics. Docking studies concerning these compounds against SARS-CoV-2 main protease showed that quercetin 3,7-O-α-L-dirhamnoside (1) and rutin (3) possessed significant binding stability at the N3 binding site in different activity degrees, which is comparable with COVID-19 main protease inhibitor, darunavir. Our study suggests that compounds quercetin 3,7-O-α-L-dirhamnoside and rutin might be potential candidates for the development of therapies against SARS-CoV-2.


Subject(s)
Antiviral Agents , COVID-19 , Coronavirus 3C Proteases/antagonists & inhibitors , Ficus , Plant Extracts , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Ficus/chemistry , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects
8.
RSC Adv ; 10(50): 29983-29998, 2020 Aug 10.
Article in English | MEDLINE | ID: covidwho-851319

ABSTRACT

3'-Hydroxy-4'-methoxy-chroman-7-O-ß-d-glucopyranoside 4 was first isolated from a natural source, together with three known compounds, the ferulic acid heptyl ester 1, naringenin 2, and 4,2',4'-trihydroxy-6'-methoxychalcone-4'-O-ß-d-glucopyranoside 3, which were isolated from peach [Prunus persica (L.) Batsch] fruits. These compounds were subjected to different virtual screening strategies in order to examine their activity to combat the COVID-19 outbreak. The study design composed of some major aspects: (a) docking with main protease (Mpro), (b) docking with spike protein, (c) 3D shape similarity study (Rapid Overlay Chemical Similarity-ROCS) to the clinically used drugs in COVID-19 patients, and finally, (d) the rule of five and the estimated pre-ADMT properties of the separated flavonoids. Docking study with Mpro of SARS-CoV-2 (PDB ID:6LU7, and 6Y2F) showed that compound 3, its aglycone part, and compound 4 have a strong binding mode to a protease receptor with key amino acids, especially Gln:166AA, and having a similar docking pose to co-crystalized ligands. Docking with the spike protein of SARS-CoV-2 illustrated that compounds 3 and 4 have a good binding affinity to PDB ID:6VSB through the formation of HBs with Asp:467A and Asn:422A. According to ROCS analysis, compounds 1, 3, and 4 displayed high similarities to drugs that prevent SARS-Co2 entry to the lung cells or block the inflammatory storm causing lung injury. Compounds 3 and 4 are good candidates for drug development especially because they showed predicted activity against SARS-CoV-2 through different mechanisms either by preventing genome replication or by blocking inflammatory storm that trigger lung injury. These compounds were isolated from peach fruit, and the study supports data and continues with the recommendation of peach fruits in controlling and managing COVID-19 cases.

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